1. Field of the Invention
The present invention relates generally to the fields of cancer, molecular medicine and drug delivery and, more specifically, to molecules that selectively home to tumor blood vessels and tumor cells.
2. Background Information
A major hurdle to advances in treating cancer is the lack of agents that are effective in selectively targeting a cancer while sparing normal tissue. Radiation therapy and surgery, for example, which generally are localized treatments, can cause substantial damage to normal tissue in the treatment field, resulting in scarring and loss of normal tissue. Chemotherapy, in comparison, which generally is administered systemically, can cause substantial damage to organs such as bone marrow, mucosa, skin and the small intestine, which undergo rapid cell turnover and continuous cell division. As a result, undesirable side effects such as nausea, loss of hair and drop in blood cell count occur as a result of systemic treatment with a chemotherapeutic agent. Such undesirable side effects often limit the amount of drug that can be safely administered, thereby hampering survival rate and impacting the quality of patient life.
Anticancer agents that target DNA are some of the most effective agents in clinical use and are responsible for significant increases in the survival of cancer patients when administered in combination with other drugs. Effective anticancer agents that target DNA include alkylating agents and agents that intercalate into DNA or result in double-stranded DNA breaks. Exemplary DNA-targeted drugs in use or clinical trial today are cyclophosphamide, melphalan, mitomycin C, bizelesin, cisplatin, doxorubicin, etoposide, mitoxantrone, actinomycin D and bleomycin (Hurley, Nature Reviews Cancer 2:188-200 (2002)). Unfortunately, like many other anti-cancer agents, DNA-targeted drugs are extremely toxic and result in significant side effects (Slapak and Kufe in Harrison=s Principles of Internal Medicine 14th Edition pages 523-537 McGraw-Hill, Inc. New York 1998). As an example, use of the platinum agent, cisplatin, can be limited by severe nausea, vomiting, neuropathy and myelosuppression.
Selective delivery of DNA-targeting drugs and other anticancer agents to tumor cells or the vasculature that supports tumor growth would result in less toxic therapy since rapidly proliferating normal cells would be spared. However, to date, it has been difficult to produce drugs that target cancer-specific genes or that are delivered specifically to cancer cells or supporting vasculature. Thus, there is a need for molecules that selectively target tumor cells and tumor vasculature. The present invention satisfies this need and also provides related advantages.